Sculptra® contains injectable poly-L-lactic acid (PLLA), a stereoisomer of polylactic acid. This is a biodegradable, biocompatible synthetic polymer, i.e. a substance consisting of macromolecules [1].

The treatment with PLLA in injectable form can now look back on more than 20 years of clinical experience, which confirms the good safety profile [2]. CE certification was obtained as early as 1999, followed by approval in the USA for lipoatrophies associated with HIV infection in 2004, and FDA approval for aesthetic use in 2009.

Significant advantages of the current formulation

The Sculptra® product now features rapid reconstitution in a two-step process [3]. This means that Sculptra® can be used immediately. In contrast, Sculptra® previously had to be rehydrated at room temperature for at least two hours, preferably overnight, and was not available for immediate use [1]. On the other hand, current clinical practice shows that the modified formulation (8 ml reconstitution volume instead of 3 ml) has significantly reduced the risk of side effects (Fig. 1).

Fig. 1: Increasing the reconstitution volume of Sculptra® leads to a reduced incidence of side effects.

The following steps should be carried out with the new reconstitution before injection:

• Remove the cap from the bottle and clean the puncture rubber (septum) with an antiseptic.
• Place an 18G needle on a sterile 5 ml disposable syringe and draw up 5 ml sterile water for injection into the syringe. Turn the bottle upside down and insert the needle through the septum. Slowly pour the sterile water into the bottle.
• Now shake vigorously for 1 minute until a homogeneous suspension is obtained.
• Add another 3 ml of sterile water and shake again until a homogeneous suspension is reached.
• Now you can use Sculptra® immediately. Alternatively, the injection solution can be stored at room temperature for up to 72 hours.

To make the implantation comfortable for the patient, 1 ml of lidocaine (2%) should be added to the injection solution immediately before the injection. In a study it was shown that immediate reconstitution does not change the physicochemical properties such as viscosity or pH [4].

Sculptra® acts as a collagen booster

Sculptra® is a biostimulant, i.e. a substance with the ability to trigger a cellular effect or tissue reaction. The controlled inflammatory reaction triggered by Sculptra® ultimately leads to new collagen production, so the firming effect of Sculptra® is based on its property as a collagen biostimulator. The loss of collagen is a key factor in the ageing process.

Collagen formation creates the structural foundation that restores a fuller appearance to the face by correcting skin quality deficiencies, including deep facial wrinkles and folds [2,5-7].

Fig. 2: 3 weeks after Sculptra® treatment, collagen accumulates and is produced by fibroblasts (shown in green).

While the fluid of the injected volume is reabsorbed within a few days, the PLLA particles remain in place. They recruit macrophages, which subsequently fuse into giant cells and in turn attract fibroblasts. The fibroblasts form the collagen that gives the skin firmness (Fig. 2). Nine months after injection, PLLA is absorbed by hydrolysis – as are all inflammatory cells. Only the newly formed collagen fibres remain at the injection site and provide an explanation for the long-lasting treatment effect (Fig. 3). In this way, Sculptra® intervenes in two decisive components of natural skin ageing: Because starting around the age of 30, not only does collagen production decrease overall [8]. In addition, collagen of reduced quality is formed.

Fig. 3: Summary of the mode of action of Sculptra®.

The increase in the formation of type I and type III collagen is also documented in a study: After three months, there was a 66.5% increase in type I collagen [9].

Sculptra®: a suitable solution for restoring skin quality and firmness

Sculptra® reactivates the skin’s natural collagen production. This leads to an increase in collagen in the skin [8,9]. Sculptra® is particularly suitable for restoring firmness to sunken areas, such as sunken cheeks caused by age-related tissue loss. Deep wrinkles and scars can also be corrected. A treatment programme usually includes 2 – 3 treatment sessions at intervals of 4 – 6 weeks, during which 1 – 2 vials can be used depending on the findings.

Compared to hyaluronic acid, there are several differences in the use of Sculptra® (Tab. 1).

Clinical study results confirm a gradual and natural collagen build-up.

There is now evidence of efficacy and safety from more than 20 studies on the use of Sculptra® [10-13].

An American study was conducted on 233 patients [13]. Compared to the comparative treatment with collagen, therapy with PLLA resulted in a consistent, gradual and significant improvement of the treated areas at all time points after week 3. The treatment effect remained practically unchanged until month 25 after the injection (see Fig. 4). This was associated with high patient satisfaction over the entire period: even after 25 months, 80% of patients still rated their results as “good” or “excellent” [14].

Fig. 4: Effect of PLLA compared to collagen on nasolabial folds (source: 13).

The most important clinical results on efficacy at a glance [9-11,13-16].

• The visible rebuilding effect of Sculptra® lasts up to two years
• Improvement is gradual, incremental and natural, as collagen production takes time to develop
• The combination with technical devices such as lasers has an additive effect: in combination treatments, it is recommended to perform Sculptra® injections first, as this stimulates fibroblast proliferation: Laser can only form new collagen from existing fibroblasts, pre-treatment optimises the laser therapy
• Treatment results are visible and noticeable for at least 25 months and are accompanied by a high level of satisfaction among patients and investigators.

Safety of the new preparation: fewer side effects thanks to higher dilution

The use of PLLA has been a proven and safe procedure for years, as long as essential principles are observed. This was the conclusion of two consensus recommendations, one from the USA, one from Europe, published in 2014 [17,18]. According to these publications, a significant further improvement in tolerability was achieved by increasing the reconstitution volume from 3 ml to 9 ml. This reduced the incidence of side effects from previously 44% [10] to 1 – 10% [19].

The most common adverse events associated with the use of Sculptra® were oedema, bruising, granulomas, product visibility or palpability (including nodules and papules) and vascular occlusion. Oedema, bruising and, in the worst case, vascular occlusion can occur with the use of any dermal filler and are not specific to PLLA treatment.

Risk of nodules – and how to deal with them

Essential for safe application is to understand the mechanism of action of Sculptra®, which is based on a foreign body reaction. Particularly in the case of errors in application such as too high a product concentration – which is largely prevented by the new formulation – or application in unsuitable regions, e.g. on the lips or lower eyelid, nodules and/or granulomas can occur, the appearance of which varies over time. It is therefore important to distinguish between early and late reactions (Fig. 5):

Fig. 5: Development of nodules and granulomas over time after injection.

Nodules have the following characteristics [20,21]:

• They are found near facial muscles especially the lips.
• The lentil- to pea-sized nodules are well demarcated by fibrous capsules.
• Resolution usually takes < 1 year
• Histologically, it is a foreign body reaction in which particles or microspheres form aggregates.
• They appear 0 – 2 months after injection.

Corticosteroids are often not helpful in clearing nodules, more effective is intralesional injection of isotonic saline and subcision.

As a rule, instructions for use were not followed when nodules appear, for example:

– Product was used too concentrated (dilution < 5 ml).

– Too much product was injected in the same area

– The interval between treatments was too short.

– There was no massaging or insufficient distribution of PLLA in the tissue

– Application in hyperkinetic regions

– The injection plane was chosen too superficially or in regions with thin dermis.

Properties of granulomas [20,21]:

• Granulomas develop 6 – 24 months after implantation.
• They grow to the size of a bean, sometimes with skin discolouration and oedema. If untreated, they disappear after 1 – 5 years.
• Histologically, it is a foreign body granuloma with giant cells, macrophages and lymphocytes (see Fig. 6).
• Their development is based on a strong inflammatory reaction
• The frequency is > 0.5%.
• An established treatment is the intralesional injection of corticosteroids (e.g. 20 – 40 mg tiramcinolone or prednisolone).

Fig. 6: Histological composition of a granuloma.

The above-mentioned difficulties can usually be avoided if the following essential points are observed when using Sculptra®:

• Inject material into different layers
• Place particles as far apart as possible
• Select suitable patients

Contraindications:

Sculptra® should not be used in the following cases:

• When active local inflammation or infection is present.
• In the area of hyperdynamic muscles (see Fig. 7)
• In patients with a history of keloids or hypertrophic scars.
• In diseases of the connective tissue
• In active immunological diseases
• During pregnancy and breastfeeding

Fig. 7: “No-go areas” for the application of Sculptra®.

Conclusion:

The new reconstitution procedure of Sculptra® offers significant advantages for physicians and patients: In contrast to the past, Sculptra® can be used immediately thanks to the new reconstitution in a two-step procedure. Due to the higher dilution, side effects of this highly efficient volume filler could be reduced to 0-10%. Because of its alternating mode of action – namely effective collagen biostimulation – Sculptra® is a significant addition to the aesthetic armamentarium in addition to hyaluronic acid. A particular advantage is the long-lasting effect of more than two years.